Induction of apoptosis by A3 adenosine receptor agonist N-(3-iodobenzyl)-adenosine-5'-N-methylcarboxamide in human leukaemia cells: a possible involvement of intracellular mechanism

Acta Physiologica
Petr Mlejnek, Petr Dolezel

Abstract

The sensitivity of cancer cells which exhibit multi-drug resistance phenotype to A3 adenosine receptor (A3AR) agonist N(6)-(3-iodobenzyl)-adenosine-5'-N-methylcarboxamide (IB-MECA) was studied. To establish direct relationship between P-glycoprotein (P-gp, ABCB1 and MDR1) expression and IB-MECA induced cell death, a straightforward method for precise estimation of intracellular level of this A3AR agonist was developed. We subjected three human leukaemia cell lines HL-60, K562 and K562/HHT to treatment with micromolar concentrations of IB-MECA. Although all cell lines used expressed A3AR, there was a large difference in their sensitivity to IB-MECA. While HL-60 and K562 cells were almost equally sensitive, the K562/HHT cells, which exhibit a multi-drug resistance phenotype because of overexpression of P-gp, were significantly more resistant. We found that the intracellular level of IB-MECA in K562/HHT cells was approx. 10 times lower than those in HL-60 or K562 cells. Inhibitors of P-gp, including cyclosporine A (CsA) and verapamil (Vpa), increased the intracellular level of IB-MECA and reversed the resistance of K562/HHT cells to this drug. Accordingly, shRNA-mediated down-regulation of P-gp significantly increased the intracel...Continue Reading

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Citations

Dec 14, 2011·Acta Physiologica·P B Persson
Aug 7, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Hamideh AbediSima Hajiahmadi
Apr 5, 2011·Expert Opinion on Investigational Drugs·Balázs KoscsóGyörgy Haskó
Jul 20, 2010·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Petr DolezelPetr Mlejnek
Aug 25, 2015·Experimental Eye Research·Joana GalvaoAna Raquel Santiago
Jun 19, 2019·Journal of Cellular Biochemistry·Petr MlejnekEliska Ruzickova
Oct 18, 2014·European Journal of Haematology·Petr KosztyuPetr Mlejnek
Jul 8, 2014·Chemico-biological Interactions·Petr Mlejnek, Petr Dolezel

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